MedKoo Biosciences

AUT1
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 565068

CAS#: 1311136-84-1

Description: AUT1 is a Kv3 potassium channel modulator which increases whole currents mediated by human Kv3.1b and Kv3.2a channels, with a concomitant leftward shift in the voltage-dependence of activation, while having a less potent effect on hKv3.3 currents.

Chemical Structure

AUT1

CAS# 1311136-84-1

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 565068
Name: AUT1
CAS#: 1311136-84-1
Chemical Formula: C18H19N3O4
Exact Mass: 341.14
Molecular Weight: 341.370
Elemental Analysis: C, 63.33; H, 5.61; N, 12.31; O, 18.75

Price and Availability

Size	Price	Availability
100mg	USD 950	Ready to ship
5mg	USD 90	Ready to ship
1g	USD 3850	Ready to ship
25mg	USD 250	Ready to ship
10mg	USD 150	Ready to ship
200mg	USD 1650	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: AUT-1; AUT 1; AUT1

IUPAC/Chemical Name: (5R)-5-Ethyl-3-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-2,4-imidazolidinedione

InChi Key: AMAOXEGBJHLCSF-CQSZACIVSA-N

InChi Code: InChI=1S/C18H19N3O4/c1-4-14-17(22)21(18(23)20-14)12-6-8-16(19-10-12)25-13-7-5-11(2)15(9-13)24-3/h5-10,14H,4H2,1-3H3,(H,20,23)/t14-/m1/s1

SMILES Code: O=C1N(C2=CC=C(OC3=CC=C(C)C(OC)=C3)N=C2)C([C@@H](CC)N1)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Product Data

Instruction:

View handling instruction

Biological target:	AUT1 is a Kv3 potassium channel modulator, with pEC50s of 5.33 and 5.31 for human recombinant Kv3.1b and Kv3.2a, respectively.
In vitro activity:	Whole cell voltage clamp recordings were performed on DCN fusiform cells, which were held at −60 mV. Stepping to voltages above −30 mV evoked large non-inactivating outward K+ currents (Fig. 2A, current at + 0 mV = 16.54 ± 10 nA, n = 4) which were reduced by approximately 50% by the perfusion of 0.5 mM TEA (Fig. 2A , 8.1 ± 3.6 nA, n = 4, P = 0.04, paired t-test). Slices were pre-incubated with AUT1 (10 μM) for 1 h. This resulted in a 65% increase in the amplitude of the K+ current at 0 mV (Fig. 2B, Control: 6.4 ± 2.3 nA, n = 6; AUT1: 10.6 ± 6.3 nA, n = 6, P = 0.02, one-sided Mann-Whitney test). Reference: Neuropharmacology. 2018 May 1; 133: 319–333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869058/
In vivo activity:	WT mice, however, that received AUT1 before amphetamine, exhibited attenuation in amphetamine-induced hyperactivity with the effects most notable at the 60 and 100 mg/kg doses. Two-way ANOVA revealed a significant main effect of treatment on locomotor activity (F(4, 67)=22.37, p<0.0001) and a genotype × treatment interaction (F(4, 67)=2.28, p=0.07; Figure 2b). At the highest dose of 100 mg/kg, AUT1 significantly decreased locomotor activity in both WT and Kv3.1-null mice before amphetamine injection, possibly indicating a nonspecific sedative effect at this dose (Figure 2a). AUT1, however, was not effective at reducing amphetamine-induced hyperactivity in mice lacking Kv3.1 channels, even at these high doses (Figure 2b and Supplementary Figure S1), arguing against a purely sedative effect. This suggests that functional Kv3.1 channels are required for the effects of AUT1 on amphetamine-induced hyperactivity. Notably, this was confirmed by repeating the experiment using Kv3.2 knockout mice where AUT1 was as effective at preventing hyperactivity as in WT mice (F(2, 24)=12.73, p=0.0002; Supplementary Figure S2). Collectively, this suggests that Kv3.1 channels (and not Kv3.2) are necessary for AUT1 mechanism of action in this model. Reference: Neuropsychopharmacology. 2018 Jan; 43(2): 435–444. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729564/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO:PBS (pH 7.2) (1:4)	0.2	0.59
	DMF	30.0	87.88
	Ethanol	5.0	14.65

Preparing Stock Solutions

The following data is based on the product molecular weight 341.370000000000000000000000000000 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Olsen T, Capurro A, Pilati N, Large CH, Hamann M. Kv3 K+ currents contribute to spike-timing in dorsal cochlear nucleus principal cells. Neuropharmacology. 2018 May 1;133:319-333. doi: 10.1016/j.neuropharm.2018.02.004. Epub 2018 Feb 5. PMID: 29421326; PMCID: PMC5869058. 2. Rosato-Siri MD, Zambello E, Mutinelli C, Garbati N, Benedetti R, Aldegheri L, Graziani F, Virginio C, Alvaro G, Large CH. A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons. J Pharmacol Exp Ther. 2015 Sep;354(3):251-60. doi: 10.1124/jpet.115.225748. Epub 2015 Jun 17. PMID: 26085652. 3. Parekh PK, Sidor MM, Gillman A, Becker-Krail D, Bettelini L, Arban R, Alvaro GS, Zambello E, Mutinelli C, Huang Y, Large CH, McClung CA. Antimanic Efficacy of a Novel Kv3 Potassium Channel Modulator. Neuropsychopharmacology. 2018 Jan;43(2):435-444. doi: 10.1038/npp.2017.155. Epub 2017 Aug 31. PMID: 28857068; PMCID: PMC5729564.
In vitro protocol:	1. Olsen T, Capurro A, Pilati N, Large CH, Hamann M. Kv3 K+ currents contribute to spike-timing in dorsal cochlear nucleus principal cells. Neuropharmacology. 2018 May 1;133:319-333. doi: 10.1016/j.neuropharm.2018.02.004. Epub 2018 Feb 5. PMID: 29421326; PMCID: PMC5869058. 2. Rosato-Siri MD, Zambello E, Mutinelli C, Garbati N, Benedetti R, Aldegheri L, Graziani F, Virginio C, Alvaro G, Large CH. A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons. J Pharmacol Exp Ther. 2015 Sep;354(3):251-60. doi: 10.1124/jpet.115.225748. Epub 2015 Jun 17. PMID: 26085652.
In vivo protocol:	1. Parekh PK, Sidor MM, Gillman A, Becker-Krail D, Bettelini L, Arban R, Alvaro GS, Zambello E, Mutinelli C, Huang Y, Large CH, McClung CA. Antimanic Efficacy of a Novel Kv3 Potassium Channel Modulator. Neuropsychopharmacology. 2018 Jan;43(2):435-444. doi: 10.1038/npp.2017.155. Epub 2017 Aug 31. PMID: 28857068; PMCID: PMC5729564.

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1: Rosato-Siri MD, Zambello E, Mutinelli C, Garbati N, Benedetti R, Aldegheri L, Graziani F, Virginio C, Alvaro G, Large CH. A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons. J Pharmacol Exp Ther. 2015 Sep;354(3):251-60. doi: 10.1124/jpet.115.225748. Epub 2015 Jun 17. PubMed PMID: 26085652. 2: Olsen T, Capurro A, Pilati N, Large CH, Hamann M. Kv3 K(+) currents contribute to spike-timing in dorsal cochlear nucleus principal cells. Neuropharmacology. 2018 May 1;133:319-333. doi: 10.1016/j.neuropharm.2018.02.004. Epub 2018 Feb 5. PubMed PMID: 29421326; PubMed Central PMCID: PMC5869058. 3: Parekh PK, Sidor MM, Gillman A, Becker-Krail D, Bettelini L, Arban R, Alvaro GS, Zambello E, Mutinelli C, Huang Y, Large CH, McClung CA. Antimanic Efficacy of a Novel Kv3 Potassium Channel Modulator. Neuropsychopharmacology. 2018 Jan;43(2):435-444. doi: 10.1038/npp.2017.155. Epub 2017 Aug 31. PubMed PMID: 28857068; PubMed Central PMCID: PMC5729564. 4: Brown MR, El-Hassar L, Zhang Y, Alvaro G, Large CH, Kaczmarek LK. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons. J Neurophysiol. 2016 Jul 1;116(1):106-21. doi: 10.1152/jn.00174.2016. Epub 2016 Apr 6. PubMed PMID: 27052580; PubMed Central PMCID: PMC4961756.

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